In U.S. Pat. Nos. 4,950,224 and 5,151,082, there are disclosed methods and apparatus for carrying out in-vivo plasmapheresis for separating plasma from other blood components within the body and blood vessels of a patient. In the apparatus pumping is used to create a trans-membrane pressure and motivate the flow of fluid from within the in-vivo system, whereby blood plasma is pumped from the patient to a treatment system such as a dialyzer or other apparatus in which toxic metabolic waste in the plasma is removed. After the plasma is treated for removal of waste products, excess fluids, toxins, and/or other deleterious plasma proteins, the treated plasma is returned and reintroduced to the patient's blood stream. Methods of toxin removal from blood using plasma, or portions of the plasma, as taught by the aforesaid patents are unique from and substantially superior to conventional hemodialysis as presently practiced for both acute and chronic kidney failure, primarily because removal of whole blood from the patient's vasculature is eliminated. The methods and apparatus described in the aforesaid patents are incorporated herein by reference.
In U.S. Pat. Nos. 6,802,820 and 6,802,971, there are disclosed specialized hollow fiber membranes which are superior in biocompatibility, performance and morphology for carrying out in-vivo plasmapheresis. In U.S. Pat. No. 6,899,692 there is disclosed a plasmapheresis filter device and catheter assembly incorporating the aforesaid specialized hollow fiber membranes. In U.S. Pat. No. 6,849,183 and U.S. patent application Ser. No. 11/078,016, filed Mar. 11, 2005 (TRANSVI.011CP1) there are disclosed apparatus and methods for therapeutic apheresis and patient fluid management, respectively, using the aforesaid specialized hollow fiber membranes, filter device and catheter assembly. Such fibers, filter device, catheter assembly, apparatus and methods as disclosed in the aforesaid patents and application are incorporated herein by reference.
In the aforesaid systems, the hollow fiber membranes function as filters, where the primary purpose of said membranes is separation of specific blood or plasma components from whole blood. In such systems, the blood (permeate) flows on the outside of the fiber and the plasma (exudate) is diffused through the fiber membrane to the interior lumen of the hollow fiber. However, as use is continued, performance of the fibers as filters becomes degraded over time. For example, clogging or fouling of the filter occurs on the surface of the filter as the pore void spaces become more occluded with particulate matter from the permeate building up within the pore void such that the minute volume of the exudate is progressively degraded to the point of failure and cessation of exudate flow. Such clogging or fouling of the filter membranes, as well as clotting problems with filter systems such as disclosed in the aforesaid patents causes major operational and economic problems with current ex-vivo systems performing Continuous Renal Replacement Therapy (CRRT) for acute and chronic kidney failure. It is reported by Ramesh, Prasad, et al., in Clinical Nephrology, Vol. 53, p. 55-60 (January 2000), that over 50% of such filters fail in 10 hours and over 75% fail in 30 hours of usage. Because short-term filter replacement is both undesirable and unacceptable, clogging or fouling failure of filters used in in-vivo systems described in the aforesaid patents would be totally unacceptable for both medical and economic reasons.